Individuals who develop diseases in association with antibodies or T lymphocytes which react with self structures are said to have autoimmunity. Autoimmune disorders, many of which are systemic connective tissue diseases, are thought to result from environmental agents acting upon genetically-susceptible hosts with subsequent immune activation and pathology. We are studying a number of these autoimmune diseases to define etiologic factors, to devise more effective therapies, and perhaps ultimately to prevent the occurrence of these diseases. Specific projects include: 1) A study of the human leukocyte antigen (HLA) and T cell receptor (TCR) genes associated with autoantibodies specific to a group of diseases, known as idiopathic inflammatory myopathies, which are characterized by chronic inflammation of muscle or myositis. The laboratory has performed molecular HLA DR, DP, and DQ gene typing by polymerase chain reactions (PCR) using sequence-specific probes and genomic DNA collected from over 200 myositis patients representing all the major clinical and autoantibody groups. There appear to be significant associations of DR-beta and DQ-alpha genes with each of the myositis-specific autoantibodies and with certain clinical groups. This project has also resulted in new PCR technology which has allowed the study of HLA types from biopsy material and human hair when blood has not been available from patients. Studies of TCR gene expression in the periphery and target organs of myositis patients using PCR are also underway. 2) Studies of the epidemiology of myositis are in progress attempting to associate clinical signs and symptoms, geographic location and season of disease-onset, and therapeutic responses in the different clinical and autoantibody subsets. A multicenter study of 377 patients has confirmed that strong associations of the above do exist, and that seasonal and geographic clustering of myositis onset occurs in groups of patients defined by myositis-specific autoantibodies.